Immune Rejection After Pancreatic Islet Cell Transplantation: In Vivo Dual Contrast-Enhanced MR Imaging in a Mouse Model

Radiology. 2013 Mar;266(3):822-30. doi: 10.1148/radiol.12121129. Epub 2012 Dec 21.

Abstract

Purpose: To detect adoptively transferred immune attack in a mouse model of islet cell transplantation by using a long-circulating paramagnetic T1 contrast agent, a protected graft copolymer (PGC) that is covalently linked to gadolinium-diethylenetriaminepentaacetic acid with fluorescein isothiocyanate (Gd-DTPA-F), which accumulates in the sites of inflammation that are characterized by vascular disruption.

Materials and methods: All animal experiments were performed in compliance with institutional guidelines and approved by the subcommittee on research animal care. Six nonobese diabetic severe combined immunodeficiency mice received transplanted human islet cells under the kidney capsule and adoptively transferred 5 × 10(6) splenocytes from 6-week-old nonobese diabetic mice. These mice also served as control subjects for comparison of pre- and postadoptive transfer MR imaging results. Mice that received phosphate-buffered saline solution only were included as nonadoptive-transfer control subjects (n = 2). In vivo magnetic resonance (MR) imaging was performed before and 17 hours after intravenous injections of PGC-Gd-DTPA-F, followed by histologic examination. Statistical differences were analyzed by means of a paired Student t test and repeated two-way analysis of variance.

Results: MR imaging results showed significantly greater accumulation of PGC-Gd-DTPA-F in the graft area after immune attack initiated by adoptive transfer of splenocytes compared with that of the same area before the transfer (T1, 137.2 msec ± 39.3 and 239.5 msec ± 17.6, respectively; P < .001). These results were confirmed at histologic examination, which showed considerable leakage of the contrast agent into the islet cell interstitium.

Conclusion: PGC-Gd-DTPA-F-enhanced MR imaging allows for the in vivo assessment of vascular damage of the graft T cell challenge.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cells, Cultured
  • Contrast Media / administration & dosage
  • Dextrans* / administration & dosage
  • Diabetes Mellitus / pathology
  • Diabetes Mellitus / surgery
  • Fluorescein-5-isothiocyanate / administration & dosage
  • Fluorescein-5-isothiocyanate / analogs & derivatives*
  • Gadolinium DTPA* / administration & dosage
  • Graft Rejection / etiology*
  • Graft Rejection / pathology*
  • Humans
  • Islets of Langerhans Transplantation / adverse effects*
  • Islets of Langerhans Transplantation / pathology*
  • Magnetic Resonance Imaging / methods*
  • Mice
  • Reproducibility of Results
  • Sensitivity and Specificity

Substances

  • Contrast Media
  • Dextrans
  • fluorescein isothiocyanate dextran
  • Fluorescein-5-isothiocyanate
  • Gadolinium DTPA